Page 172 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 5-9 Integumentary System

Endemic locations
PEMPHIGUS FOLIACEUS
Cuba
Pemphigus foliaceus is a chronic autoimmune blistering Dominican Republic
disease. Pemphigus foliaceus can be seen in an isolated Mexico Belize Jamaica Puerto Rico
form or as an endemic form called fogo selvagem. These Honduras Haiti
diseases are caused by autoantibody production against Guatemala Nicaragua Guyana
desmosomal proteins. The endemic form of the disease El Salavador Panama Surinam
is seen in small regions in the jungles of South America, Costa Rica Venezuela French Guiana
predominantly in Brazil. Pemphigus foliaceus is closely Colombia
related to pemphigus vulgaris, and in some cases the
clinical picture and antibody profile can shift from one Ecuador
disease to the other, leading to difficulty in classification.
Clinical Findings: Pemphigus foliaceus is a rare
disease that most frequently affects patients who are
about 50 years of age. There is no sex or race predilec- Brazil
tion. Blistering of the skin is prominent and can affect Peru
large body surface areas. The blisters tend to be more Bolivia
superficial than those of pemphigus vulgaris. The blis-
ters are rarely found intact because of their superficial
and fragile nature. Mucous membranes are rarely Chile
affected, because the mucocutaneous surfaces do not
contain high concentrations of the desmoglein 1
protein. Patients exhibit a positive Nikolsky’s sign. This Paraguay
sign is positive when exertion of pressure (rubbing) Widespread super-
induces a blister or erosion on nonaffected skin. Uruguay ficial erosions
Fogo selvagem (Portuguese for “wild fire”) affects a Argentina characteristic of the
younger population, occurring in patients approxi- pemphigus group
mately 25 years of age. It is believed to be transmitted of diseases. Rarely
by the bite of the black fly or the mosquito in patients intact bullae or
who are susceptible to the disease. It has been postulated vesicles are found.
that the bite begins a cascade of immune system anti-
body production, resulting in formation of the patho-
genic antibodies against desmoglein 1. The infectious
agent transmitted by the flies has not been discovered. Major areas
A fair percentage of patients have a family member who Minor areas
is also affected, and this provides some clinical evidence
for a genetic predisposition to the disease. The disease
exhibits photosensitivity in the ultraviolet B range.
Indirect immunofluorescence testing of the patient’s
serum shows autoantibodies against desmoglein 1.
Histology: The histological findings of pemphigus
foliaceus and its endemic form, fogo selvagem, are
identical. Intraepidermal blistering is caused by acan-
tholysis. The acantholysis is most prominent in the Direct immuno-
upper epidermis, usually starting in the granular cell fluorescence showing
layer and above. Typically, a mixed inflammatory infil- uniform staining
trate is seen within the dermis. Varying amounts of between keratinocytes
crust and superficial bacteria are seen in areas of chronic in the dermis. The
erosion. Immunofluorescence staining shows a fishnet antibody is directed
pattern of intercellular staining with immunoglobulin against the desmo-
G and complement. glein 1 protein.
Pathogenesis: Abnormal antibody production is
directed against the desmoglein 1 protein, which is a
critical component of the desmosomal attachment
between adjacent keratinocytes. Desmogleins are
calcium-dependent adhesion proteins known as cadher-
ins. As the autoantibodies attach to the desmoglein
protein and are deposited within the epidermis, they
activate complement. Complement activation, along
with the cytotoxic effects of lymphocytes, leads to acan-
tholysis of keratinocytes and the eventual blistering of the mainstay of therapy, and combinations are occa- pemphigus foliaceus requires chronic therapy, because
the epidermis. The hemidesmosome is unaffected, and sionally required to get the disease under control. Oral this is a chronically relapsing and remitting disease.
the basilar layer of keratinocytes stays attached to the corticosteroids are typically the first medications used, Supportive care is required to avoid excessive trauma
basement membrane zone. along with a steroid-sparing agent. Azathioprine, myco- and friction to the skin, which can induce blistering.
Treatment: Because mucous membrane involvement phenolate mofetil, cyclophosphamide, and rituximab Bacterial superinfection needs to be treated promptly.
is almost nonexistent and the blistering is more super- have all been used with varying success. Intravenous Therapy for fogo selvagem is similar in many
ficial, the course of pemphigus foliaceus is typically less immunoglobulin (IVIG) has also been used. Use of respects. The use of mosquito and fly control measures
severe than that of pemphigus vulgaris; however, this is the non-immunosuppressive agents, tetracycline and may be of help in the endemic regions, because these
not always the case. Therapy is directed toward decreas- nicotinamide, has shown variable success. The same can insects are believed to be the vectors of transmission to
ing the antibody formation. Immunosuppressants are be said of hydroxychloroquine. The treatment of susceptible humans.

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